Accumulating anatomical, electrophysiological and pharmacological data on the gustatory and visceral pathways suggest several testable hypotheses about the functional organization of the gustatory zone of the nucleus of the solitary tract (NST). During the previous funding period, the PI's laboratory has shown that taste cells in the NST are influenced by several neurotransmitters and modulators, including excitatory amino acids (EAAs), gamma-aminobutyric acid (GABA), substance P (SP), and met-enkephalin (ENK), and that taste neurons in the NST are excited or inhibited by centrifugal inputs from the ipsilateral insular cortex (IC) and the lateral hypothalamus (LH) and central nucleus of the amygdala (CeA) bilaterally. This proposal seeks funding t o extend these findings in significant ways. T he first Specific Aim is to investigate descending influences of the contralateral IC and the bed nucleus of the stria terminalis (BNST), another source of descending input to the NST, and to determine the effects of centrifugal modulation on gustatory neural coding. These extracellular neurophysiological experiments test hypotheses that the contralateral IC and the BNST also modulate taste input and that different forebrain regions (IC, LH, CeA and BNST) differentially alter the neural representation of taste quality. They also test the hypothesis that NST neurons projecting to the parabrachial nuclei (PbN) are targeted differently by centrifugal inputs than local-circuit neurons. The second Specific Aim addresses the role of EAAs, GABA, SP and opioids in the excitatory and inhibitory modulation of NST neurons. These experiments test hypotheses that excitatory centrifugal modulation is mediated via EAAs or SP, whereas GABAergic or opioid mechanisms mediate inhibitory influences. Immunocytochemical studies address the hypothesis that PbN-projection neurons express different neurotransmitter receptors than local-circuit neurons. The third Specific Aim employs in vivo intracellular recording to determine the role of different morphological and electrophysiological neuron types in the NST in these modulatory circuits. These experiments test hypotheses that all neuron types in the rostral NST are gustatory and that different neuron types express different neurotransmitter receptors and are differentially targeted by centrifugal neurons. These in vivo experiments are designed to reveal how synaptic interactions in the NST and connections to and from this nucleus interact to control the responses of NST neurons to gustatory input. These studies will provide new information to our understanding of the functional organization of the central gustatory system.